Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH prevents genomic instability from stalled replication forks
作者： A. Motegi , H.-J. Liaw , K.-Y. Lee , H. P. Roest , A. Maas
关键词:
摘要: Chronic stalling of DNA replication forks caused by damage can lead to genomic instability. Cells have evolved lesion bypass pathways such as postreplication repair (PRR) resolve these arrested forks. In yeast, one branch PRR involves proliferating cell nuclear antigen (PCNA) polyubiquitination mediated the Rad5-Ubc13-Mms2 complex that allows a template-switching mechanism. Previously, we identified human SHPRH functional homologue yeast Rad5 and revealed existence RAD5-like pathway in cells. Here report identification HLTF second RAD5 HLTF, like SHPRH, shares unique domain architecture with promotes lysine 63-linked PCNA. Similar Rad5, is able interact UBC13 PCNA, well SHPRH; reduction either or expression enhances spontaneous mutagenesis. Moreover, Hltf-deficient mouse embryonic fibroblasts show elevated chromosome breaks fusions after methyl methane sulfonate treatment. Our results suggest are homologues cooperatively mediate PCNA maintain stability.
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